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2015 ; 6
(ä): 158
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Negative Regulation of Humoral Immunity Due to Interplay between the SLAMF1,
SLAMF5, and SLAMF6 Receptors
#MMPMID25926831
Wang N
; Halibozek PJ
; Yigit B
; Zhao H
; O'Keeffe MS
; Sage P
; Sharpe A
; Terhorst C
Front Immunol
2015[]; 6
(ä): 158
PMID25926831
show ga
Whereas the SLAMF-associated protein (SAP) is involved in differentiation of T
follicular helper (Tfh) cells and antibody responses, the precise requirements of
SLAMF receptors in humoral immune responses are incompletely understood. By
analyzing mice with targeted disruptions of the Slamf1, Slamf5, and Slamf6 genes,
we found that both T-dependent and T-independent antibody responses were twofold
higher compared to those in single knockout mice. These data suggest a
suppressive synergy of SLAMF1, SLAMF5, and SLAMF6 in humoral immunity, which
contrasts the decreased antibody responses resulting from a defective GC reaction
in the absence of the adapter SAP. In adoptive co-transfer assays, both
[Slamf1?+?5?+?6] (-/-) B and T cells were capable of inducing enhanced antibody
responses, but more pronounced enhancement was observed after adoptive transfer
of [Slamf1?+?5?+?6] (-/-) B cells compared to that of [Slamf1?+?5?+?6] (-/-) T
cells. In support of [Slamf1?+?5?+?6] (-/-) B cell intrinsic activity,
[Slamf1?+?5?+?6] (-/-) mice also mounted significantly higher antibody responses
to T-independent type 2 antigen. Furthermore, treatment of mice with anti-SLAMF6
monoclonal antibody results in severe inhibition of the development of Tfh cells
and GC B cells, confirming a suppressive effect of SLAMF6. Taken together, these
results establish SLAMF1, SLAMF5, and SLAMF6 as important negative regulators of
humoral immune response, consistent with the notion that SLAM family receptors
have dual functions in immune responses.
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